Interkingdom signaling by structurally related cyanobacterial and algal secondary metabolites

Several groups of structurally-related compounds, comprised of either five or six-membered ring structures with attached lipophilic carbon chains and in some cases possessing halogen atoms, have been isolated from various marine algae and filamentous cyanobacteria. The related compounds considered in the present work include the coibacins, laurenciones, honaucins, malyngamides and the tumonoic acids. Members of all of these compound families were assayed and found to inhibit the production of nitric oxide in lipopolysaccharides-stimulated macrophages, indicating their anti-inflammatory potential. In addition, several of these same marine natural products were found to inhibit quorum sensing mediated phenotypes in Vibrio harveyi BB120 and/or Escherichia coli JB525. The mechanism and evolutionary significance for inhibition of these cellular processes in prokaryotic and eukaryotic systems are speculated on and discussed.     

Phylogenetic Inferences Reveal a Large Extent of Novel Biodiversity in Chemically Rich Tropical Marine Cyanobacteria

Benthic marine cyanobacteria are known for their prolific biosynthetic capacities to produce structurally diverse secondary metabolites with biomedical application and their ability to form cyanobacterial harmful algal blooms. In an effort to provide taxonomic clarity to better guide future natural product drug discovery investigations and harmful algal bloom monitoring, this study investigated the taxonomy of tropical and subtropical natural product-producing marine cyanobacteria on the basis of their evolutionary relatedness. Our phylogenetic inferences of marine cyanobacterial strains responsible for over 100 bioactive secondary metabolites revealed an uneven taxonomic distribution, with a few groups being responsible for the vast majority of these molecules. Our data also suggest a high degree of novel biodiversity among natural product-producing strains that was previously overlooked by traditional morphology-based taxonomic approaches. This unrecognized biodiversity is primarily due to a lack of proper classification systems since the taxonomy of tropical and subtropical, benthic marine cyanobacteria has only recently been analyzed by phylogenetic methods. This evolutionary study provides a framework for a more robust classification system to better understand the taxonomy of tropical and subtropical marine cyanobacteria and the distribution of natural products in marine cyanobacteria.     

Ion mobility mass spectrometry enables the efficient detection and identification of halogenated natural products from cyanobacteria with minimal sample preparation

Direct observation of halogenated natural products produced by different strains of marine cyanobacteria was accomplished by electrospray ionization and matrix assisted laser desorption ionization and gas phase separation via ion mobility mass spectrometry of extracts as well as intact organisms.     

Cyanobacteria-shrimp colonies in the Mariana Islands

Aquatic Ecology - Cyanobacteria have multifaceted ecological roles on coral reefs. Moorena bouillonii, a chemically rich filamentous cyanobacterium, has been characterized as a pathogenic organism...     

Underestimated biodiversity as a major explanation for the perceived rich secondary metabolite capacity of the cyanobacterial genus Lyngbya

Marine cyanobacteria are prolific producers of bioactive secondary metabolites responsible for harmful algal blooms as well as rich sources of promising biomedical lead compounds. The current study focused on obtaining a clearer understanding of the remarkable chemical richness of the cyanobacterial genus Lyngbya. Specimens of Lyngbya from various environmental habitats around Curaçao were analysed for their capacity to produce secondary metabolites by genetic screening of their biosynthetic pathways. The presence of biosynthetic pathways was compared with the production of corresponding metabolites by LC‐ESI‐MS² and MALDI‐TOF‐MS. The comparison of biosynthetic capacity and actual metabolite production revealed no evidence of genetic silencing in response to environmental conditions. On a cellular level, the metabolic origin of the detected metabolites was pinpointed to the cyanobacteria, rather than the sheath‐associated heterotrophic bacteria, by MALDI‐TOF‐MS and multiple displacement amplification of single cells. Finally, the traditional morphology‐based taxonomic identifications of these Lyngbya populations were combined with their phylogenetic relationships. As a result, polyphyly of morphologically similar cyanobacteria was identified as the major explanation for the perceived chemical richness of the genus Lyngbya, a result which further underscores the need to revise the taxonomy of this group of biomedically important cyanobacteria.     

Chemical variation in the tropical seaweed Stypopodium zonale (dictyotaceae)

Five separate collections of the tropical seaweed Stypopodium zonale were analysed for ten secondary metabolites using a combination of high performance liquid chromatography and proton nuclear magnetic resonance spectrometry. Shallow water populations from the Caribbean were found to possess similar metabolite profiles from year to year and from widely diverse locations. Stypopodium zonale from the South Pacific (Palau) contained similar structure types; however, the profile was qualitatively and quantitatively dissimilar to the Caribbean algae. A deep water Caribbean form of S. zonale was found to contain two metabolites, epitaondiol and 6a-desmethyl-6-acetylatomaric acid, not observed in the other extracts. This latter population is morphologically and anatomically distinct from the other S. zonale Caribbean populations.     

Discovery of 12-(S)-hydroxy-5,8,10,14-icosatetraenoic acid [12-(S)-HETE] in the tropical red alga Platysiphonia miniata

The potent mammalian immunohormone, 12-(S)-hydroxy-5,8,10,14-icosatetraenoic acid (12-(S)-HETE), is a 12-lipoxygenase metabolite of arachidonic acid that is widely distributed in animal tissues. In humans, it is produced and secreted by platelet cells and elicits both chemotactic and degranulatory responses in target neutrophils. As widely as 12-lipoxygenase activity and one of its major products, 12-(S)-HETE, have been found in animal tissues, it has never been found in plants. Herein, we report the first isolation of the 12-lipoxygenase product, 12-(S)-HETE, from a plant, the tropical marine alga Platysiphonia miniata (C. Agardh) B?rgesen.     

Phenolic lipids from related marine algae of the order dictyotales

2-(1′-Oxo-dodeca-5′, 8′, 11′, 14′, 17′(all Z)-pentaenyl)-5-methoxy-1, 3-dihydroxybenzene, 2- (1′-oxo-dodeca-5′, 8′, 11′, 14′, 17′(all Z)-pentaenyl)-1, 3, 5-trihydroxybenzene, 2-(17′-hydroxy-1′-oxo-dodeca-5′, 8′, 11′, 14′(all Z)-tetraenyl)-1, 3, 5-trihydroxybenzene and 2-(1′oxo-hexadecyl)-1, 3, 5-trihydroxybenzene have been isolated from the related brown algae Zonaria farlowii, Z diesingiana and Lobophora papenfussii. The structures of these new metabolites are based on extensive spectral analyses and comparisons with model compounds. The isolation of (+)-7, 8-dimethyltocol, from L. papenfussii, is also reported.     

Significant natural product biosynthetic potential of actinorhizal symbionts of the genus frankia, as revealed by comparative genomic and proteomic analyses

Bacteria of the genus Frankia are mycelium-forming actinomycetes that are found as nitrogen-fixing facultative symbionts of actinorhizal plants. Although soil-dwelling actinomycetes are well-known producers of bioactive compounds, the genus Frankia has largely gone uninvestigated for this potential. Bioinformatic analysis of the genome sequences of Frankia strains ACN14a, CcI3, and EAN1pec revealed an unexpected number of secondary metabolic biosynthesis gene clusters. Our analysis led to the identification of at least 65 biosynthetic gene clusters, the vast majority of which appear to be unique and for which products have not been observed or characterized. More than 25 secondary metabolite structures or structure fragments were predicted, and these are expected to include cyclic peptides, siderophores, pigments, signaling molecules, and specialized lipids. Outside the hopanoid gene locus, no cluster could be convincingly demonstrated to be responsible for the few secondary metabolites previously isolated from other Frankia strains. Few clusters were shared among the three species, demonstrating species-specific biosynthetic diversity. Proteomic analysis of Frankia sp. strains CcI3 and EAN1pec showed that significant and diverse secondary metabolic activity was expressed in laboratory cultures. In addition, several prominent signals in the mass range of peptide natural products were observed in Frankia sp. CcI3 by intact-cell matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). This work supports the value of bioinformatic investigation in natural products biosynthesis using genomic information and presents a clear roadmap for natural products discovery in the Frankia genus.